研究领域

Bioorganic/Chemical Biology/Organic

Stuart Schreiber's lab studies the science of therapeutics. Researchers in his group rely on human biology to identify therapeutic targets that have been validated prior to testing in humans, and chemistry and chemical biology to discover small molecules that modulate the targets in ways required to provide relief or protection from disease. Schreiber and his group members have discovered principles that underlie information transfer and storage in cells, specifically discoveries relating to signaling by the phosphatase calcineurin and kinase mTOR (demonstrating for the first time that drugs can result from the targeting of protein kinases and protein phosphatases), gene regulation by chromatin-modifying histone deacetylases, small-molecule dimerizers that activate cellular processes by enforced proximity, and small-molecule probes of challenging targets and processes (e.g., transcription factors, oncogenes, protein/protein interactions, transdifferentiation) that relate to human disease. Their work has contributed to diversity-oriented synthesis (DOS) and discovery-based small-molecule screening in an open data-sharing environment.

近期论文

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"Diversity-Oriented Synthesis Yields A New Lead for Treatment of Chagas Disease" Sivaraman Dandapani, Andrew R. Germain, Ivan Jewett, Sebastian le Quement, Jean-Charles Marie, Giovanni Muncipinto, Jeremy R. Duvall, Leigh C. Carmody, Jose R. Perez, Juan C. Engel, Juan Gut, Jiri Keller, Danielle de Siqueira Neto, Jair Lage, McKerrow James, Kaiser Marce, Rodriguez Ana, Palmer Michelle, Foley Michael, Schreiber Stuart, Munoz, Benito, ACS Med. Chem. Lett., 2014, 5, 149-153. "Lenalidomide promotes CRBN-mediated ubiquitination and degradation of IKZF1 and IKZF3" Jan Kronke, Namrata Udeshi, Anupama Narla, Peter Grauman, Slater N. Hurst, Marie McConkey, Tanya Svinkina, Dirk Heckl, Eamon Comer, Monica Schenone, Stuart L. Schreiber, Steven A. Carr, Benjamin L. Ebert, Science, 2014, 343, 301-305. "Regulation of ferroptotic cancer cell death by GPX4" Wan Seok, Yang, Rohitha SriRamaratnam, Matthew E. Welsch, Kenichi Shimada, Rachid Skouta, Vasanthi S. Viswanathan, Jaime H. Cheah, Paul A. Clemons, Alykhan F. Shamji, Clary B. Clish, Lewis M. Brown, Albert W. Girotti, Virginia W. Cornish, Stuart L. Schreiber, Brent R. Stockwell, Cell, 2014, 156, 317-331. "Quantitative-proteomic comparison of alpha and beta cells to uncover novel targets for lineage reprogramming" Amit Choudhary, Kaihui Hu He, Philipp Mertins, Namrata D. Udeshi, Vlado Dancik, Dina Fomina-Yadlin, Stefan Kubicek, Paul A. Clemons, Stuart L. Schreiber, Steven A. Carr, Bridget K. Wagner, PLoS ONE, 2014, 9, e95914. "Automated structure?activity relationship mining: connecting chemical structure to biological profiles" Mathias J. Wawer, David E. Jaramillo, Vlado Dancik, Daniel M. Fass, Stephen J. Haggarty, Alykhan F. Shamji, Bridget K. Wagner, Stuart L. Schreiber, Paul A. Clemons, J. Biomolecular Screening, 2014, 19, 738-748. "Atg16L1 T300A variant decreases selective autophagy resulting in altered cytokine signaling and decreased antibacterial defense" Kara G. Lassen, Petric Kuballa, Kara L. Conway, Khushbu K. Patel, Christine E. Becker, Joanna M. Peloquin, Eduardo J. Villablanca, Jason M. Norman, Ta-Chiang Liu, Robert J. Heath, Morgan L. Becker, Lola Fagbami, Heiko Horn, Johnathan Mercer, Omer H. Yilmaz, Jacob D. Jaffe, Alykhan F. Shamji, Atul K. Bhan, Steven A. Carr, Mark J. Daly, Herbert W. Virgin IV, Stuart L. Schreiber, Thaddeus S. Stappenbeck, Ramnik J. Xavier, Proc. Natl. Acad. Sci., U.S.A, 2014, 111, 7741-7746. "Toward performance-diverse small-molecule libraries for cell-based phenotypic screening using multiplexed high-dimensional profiling" Mathias J. Wawer, Kejie Li, Sigrun M. Gustafsdottir, Vebjorn Ljosa, Nicole E. Bodycombe, Melissa Parkin, Katherine L. Sokolnicki, Mark-Anthony Bray, Melissa M. Kemp, Ellen Winchester, Bradley Taylor, George B. Grant, C. Suk-Yee Hon, Jeremy R. Duvall, J. Anthony Wilson, Joshua A. Bittker, Vlado Danč?k, Rajiv Narayan, Aravind Subramanian, Wendy Winckler, Todd R. Golub, Anne E. Carpenter, Alykhan F. Shamji, Stuart L. Schreiber, Paul A. Clemons, Proc. Natl. Acad. Sci., U.S.A., 2014, 111, 10911-10916. "Identification of Inhibitors of PvdQ, an Enzyme Involved in the Synthesis of the Siderophore Pyoverdine" Jacqueline M. Wurst, Eric J. Drake, Jimmy R. Theriault, Ivan Jewett, Lynn VerPlank, Jose R. Perez, Sivaraman Dandapani, Michelle Palmer, Samuel M. Moskowitz, Stuart L. Schreiber, Benito Munoz, Andrew M. Gulick, A.C.S. Chem. Biol., 2014, 9, 1536-1544. "Small-molecule screening identifies inhibition of salt-inducible kinases as a therapeutic strategy to enhance immunoregulatory functions of dendritic cells" Thomas B. Sundberg, Hwan Geun Choi, Joo-Hye Song, Caitlin N. Russell, Mahmud M. Hussain, Daniel B. Graham, Bernard Khor, John Gagnon, Kavitha Narayan, Vlado Dancik, Jose R. Perez, Hans-Christian Reinecker, Nathanael S. Gray, Ramnik J. Xavier, Stuart L. Schreiber, Alykhan F. Shamji, Proc. Natl. Acad. Sci., U.S.A., 2014, 111, 12468-12473. "NAMPT is the cellular target of STF-31-like small-molecule probes" Drew J. Adams, Daisuke Ito, Matthew Rees, Brinton Seashore-Ludlow, Xiaoling Puyang, Alex Ramos, Jaime Cheah, Paul A. Clemons, Markus Warmuth, Ping Zhu, Alykhan F. Shamji, Stuart L. Schreiber, A.C.S. Chem. Biol., 2014, 9, 2247-2254. "Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Towards the Development of Novel Antimalarial Agents" Eamon Comer, Jennifer Beaudoin, Nobutaka Kato, Mark Fitzgerald, Richard Heidebrecht, Maurice duPont Lee, Daniela Masi, Marion Mercier, Carol Mulrooney, Giovanni Muncipinto, Ann Rowley, Keila N Crespo Llado, Adelfa E Serrano Brizuela, Michelle A Palmer, Michael Foley, Benito Munoz, Christina Scherer, Jeremy Duvall, Stuart Schreiber, J. Med. Chem., 2014, 57, 8496-8502. "Dilazep Analogues for the Study of Equilibrative Nucleoside Transporters 1 and 2 (ENT1 and ENT2)" Hilaire Playa, Timothy A. Lewis, Amal Ting, Byung-Chul Suh, Benito Munoz, Robert Matuza, Brent J. Passer, Stuart L. Schreiber, John K. Buolamwini, Bioorg. Med. Chem. Lett., 2014, 24, 5801-5804. "BioAssay Research Database (BARD): chemical biology and probe development enabled by structured metadata and result types" Eleanor A. Howe, Andrea de Souza, David Lahr, Simon Chatwin, Philip Montgomery, Benjamin Alexander, Dac-Trung Nguyen, Yasel Cruz, Derek Stonich, Gil Walzer, Jason Rose, Shaita Picard, Zihan Liu, Jaime Rose, Xiaorong Xiang, Jacob Aseidu, Daniel Durkin, Jeri Levine, Jeremy Yang, Stephan Schurer, John Braisted, Noel Southall, Mark Southern, Thomas Chung, Steve Brudz, Cordelle Tanega, Stuart L. Schreiber, Joshua A. Bittker, Rajarshi Guha, Paul A. Clemons, Nucleic Acid Research, 2014 "Syntheses and Discovery of a Novel Class of Cinnamic Hydroxamates as Histone Deacetylase (HDAC) Inhibitors by Multimodality Molecular Imaging in Living Subjects" Carmel Chan, Jun Qi, Billy Smith, Ronald Paranal, James Bradner, Ralpha Mazitschek, Nathan West, Robert Reeves, Gabriela Chiosis, Stuart Schreiber, Paulmurugan Ramasamy, and Sanjiv Sam Gambhir, Cancer Research, 2014, 74, 7475-7486. "Target-Based Identification of Whole-Cell Active Inhibitors of Biotin Biosynthesis in Mycobacterium tuberculosis" Sae Woong Park, Dominick E. Casalena, Daniel J. Wilson, Ran Dai, Partha P. Nag, Feng Liu, Jim P. Boyce, Joshua A. Bittker, Stuart L. Schreiber, Barry C. Finzel, Dirk Schnappinger, Courtney C. Aldrich, Chem & Biol, 2015, 22, 76-86. "Synthesis of Oxazocenones via Gold(I)-Catalyzed 8-Endo-Dig Hydroalkoxylation of Alkynamides" Stephen S. Scully, Shao-Liang Zheng, Bridget K. Wagner, Stuart L. Schreiber, Org. Lett., 2015, 17, 418-421. "Small-molecule control of cytokine function: new opportunities for treating immune disorders" Thomas B. Sundberg, Ramnik J. Xavier, Stuart L. Schreiber, Alykhan F. Shamji, Curr Opinion Chem Biol, 2015, in press. "Diversity-Oriented Synthesis probe targets Plasmodium falciparum cytochrome b ubiquinone reduction site and synergizes with oxidation site inhibitors" Amanda K. Lukens, Richard W. Heidebrecht, Jr, Carol Mulrooney, Jennifer A. Beaudoin, Eamon Comer, Jeremy R. Duvall, Mark E. Fitzgerald, Daniela Masi, Leila S. Ross, Kevin Galinsky, Christina A. Scherer, Michelle Palmer, Benito Munoz, Michael Foley, Stuart L. Schreiber, Roger C. Wiegand, Dyann F. Wirth, J. Infectious Disease, 2015, in press. "Niche-Based Screening in Multiple Myeloma Identifies a Novel Kinesin-5 Inhibitor with Improved Selectivity over Hematopoietic Progenitors" Shrikanta Chattopadhyay, Alison L. Stewart, Siddhartha Mukherjee, Cherrie Huang, Kimberly A. Hartwell, Peter G. Miller, Radhika Subramanian, Leigh C. Carmody, Rushdia Z. Yusuf, David B. Sykes, Joshiawa Paulk, Amedeo Vetere, Sonia Vallet, Loredana Santo, Diana D. Cirstea, Teru Hideshima, Vlado Dancik, Max Majireck, Mahmud Hussain, Shambhavi Singh, Ryan Quiroz, Jonathan Iaconelli, Rakesh Karmacharya, Nicola J. Tolliday, Paul A. Clemons, Tarun M. Kapoor, Malcolm A.S. Moore, Andrew M. Stern, Alykhan F. Shamji, Benjamin L. Ebert, Todd R. Golub, Noopur S. Raje, David T. Scadden, Stuart L. Schreiber, Cell Reports, 2015, in press. "Linking tumor mutations to drug responses via a quantitative chemical-genetic interaction map" Maria M. Martins, Alicia Y. Zhou, Alexandra Corella, Dai Horiuchi, Christina Yau, Taha, Rakshandehroo, John D. Gordan, Rebecca S. Levin, Jeff Johnson, John Jascur, Mike Shales, Antonio Sorrentino, Jaime Cheah, Paul A. Clemons, Alykhan F. Shamji, Stuart L. Schreiber, Nevan J. Krogan, Kevan M. Shokat, Frank McCormick, Andrei Goga, Sourav Bandyopadhyay, Cancer Discovery, 2015, in press. "HDAC6 Inhibition Increases Membrane Localization Of β-Catenin In Human iPSC-derived Neural Progenitor Cells By Modulating Lys-49 Acetylation" Jonathan Iaconelli, Joanne H. Huang, Shaunna S. Berkovitch, Shrikanta Chattopadhyay, Ralph Mazitschek, Stuart L. Schreiber, Stephen J. Haggarty, Rakesh Karmacharya, , ACS Chem. Biol., 2015, 10, xxx-yyy.